Pepsin-mediated processing of the cytoplasmic histone H2A to strong antimicrobial peptide buforin I

被引:90
作者
Kim, HS
Yoon, H
Minn, I
Park, CB
Lee, WT
Zasloff, M
Kim, SC
机构
[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Yusong Gu, Taejon 305701, South Korea
[2] Pochon Cha Univ, Coll Med, Dept Anat, Kyonggi Do, South Korea
[3] Yonsei Univ, Coll Med, Dept Anat, Seoul, South Korea
[4] Magainin Pharmaceut Inc, Plymouth Meeting, PA 19462 USA
关键词
D O I
10.4049/jimmunol.165.6.3268
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The intestinal epithelium forms a first line of innate host defense by secretion of proteins with antimicrobial activity against microbial infection. Despite the extensive studies on the antimicrobial host defense in many gastrointestinal tracts, little is known about the antimicrobial defense system of the stomach. The potent antimicrobial peptide buforin I, consisting of 39 aa, was isolated recently from the stomach tissue of an Asian toad, Bufo bufo gargarizans, In this study we examined the mechanism of buforin I production in toad stomach tissue. Buforin I is produced by the action of pepsin isozymes, named pepsin Ca and Cb, cleaving the Tyr(39)-Ala(40) bond of histone H2A. Immunohistochemical analysis revealed that buforin I is present extracellularly on the mucosal surface, and unacetylated histone H2A, a precursor of buforin I, is localized in the cytoplasm of gastric gland cells. Furthermore, Western blot analysis showed that buforin I is also present in the gastric fluids, and immunoelectron microscopy detected localization of the unacetylated histone H2A in the cytoplasmic granules of gastric gland cells. The distinct subcellular distribution of the unacetylated histone H2A and the detection of the unacetylated buforin I both on the mucosal surface and in the lumen suggest that buforin I is produced from the cytoplasmic unacetylated histone H2A secreted into the gastric lumen and subsequently processed by pepsins, Our results indicate that buforin I along with pepsins in the vertebrate stomach may contribute to the innate host defense of the stomach against invading microorganisms.
引用
收藏
页码:3268 / 3274
页数:7
相关论文
共 45 条
[1]  
ATKINSON MJ, 1985, J IMMUNOL, V135, P2524
[2]   HISTONE H4-RELATED OSTEOGENIC GROWTH PEPTIDE (OGP) - A NOVEL CIRCULATING STIMULATOR OF OSTEOBLASTIC ACTIVITY [J].
BAB, I ;
GAZIT, D ;
CHOREV, M ;
MUHLRAD, A ;
SHTEYER, A ;
GREENBERG, Z ;
NAMDAR, M ;
KAHN, A .
EMBO JOURNAL, 1992, 11 (05) :1867-1873
[3]  
BILOZUR ME, 1990, J BIOL CHEM, V265, P19697
[4]   PEPTIDE ANTIBIOTICS AND THEIR ROLE IN INNATE IMMUNITY [J].
BOMAN, HG .
ANNUAL REVIEW OF IMMUNOLOGY, 1995, 13 :61-92
[5]  
BOMAN HG, 1989, J BIOL CHEM, V264, P5852
[6]   Extracellularly occurring histone H1 mediates the binding of thyroglobulin to the cell surface of mouse macrophages [J].
Brix, K ;
Summa, W ;
Lottspeich, F ;
Herzog, V .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (02) :283-293
[7]   Histones in transit: Cytosolic histone complexes and diacetylation of H4 during nucleosome assembly in human cells [J].
Chang, L ;
Loranger, SS ;
Mizzen, C ;
Ernst, SG ;
Allis, CD ;
Annunziato, AT .
BIOCHEMISTRY, 1997, 36 (03) :469-480
[8]  
FOLTMANN B, 1981, ESSAYS BIOCHEM, V17, P52
[9]   PURIFICATION AND CHARACTERIZATION OF PEPSINOGENS AND A UNIQUE PEPSIN FROM RAT STOMACH [J].
FURIHATA, C ;
SAITO, D ;
FUJIKI, H ;
KANAI, Y ;
MATSUSHIMA, T ;
SUGIMURA, T .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1980, 105 (01) :43-50
[10]   The relationship between acid stress responses and virulence in Salmonella typhimurium and Listeria monocytogenes [J].
Gahan, CGM ;
Hill, C .
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY, 1999, 50 (1-2) :93-100